INTRODUCTION
Childhood asthma is the most common chronic disease in childhood and a significant public health problem in the U.S. as well as in many other countries1. Despite relatively recent advances in our understanding of the inflammatory nature of the disease and the availability of highly effective medications to control their symptoms, many pediatric patients continue to experience poor asthma control with recurrent disease exacerbations2.
Acute asthma has a significant impact not only on the utilization of health care and the quality of life of children and their families but also on a large percentage of disease costs3. Recent international evidence-based asthma clinical practice guidelines recommend the use of inhaled beta-2 agonists (SABA) and systemic corticosteroids (SC) as the first-line agents for acute asthma4,5. The efficacy of SC in acute asthma is well established, with a positive impact on several clinically meaningful outcomes, such as hospital admission rate, symptom scores, and the number of relapses after discharge from the emergency department (ED)6. However, the fact that despite SC use many children still require admission to hospital and that SCs have a slow onset of action (3–4 h after their administration) is a cause of concern among ED teams7.
For this reason, the use of other anti-inflammatory therapies such as inhaled corticosteroids (ICS) for the treatment of acute asthma has been explored6. Potential benefits of ICS in acute asthma therapy might include a rapid onset of action and a significant efficacy in diminishing airway reactivity and edema because of their direct delivery to the airways8. This is mainly because ICS, but not SC, cause immediate local bronchial mucosal vasoconstriction and inhibition of edema formation mediated by non-genomic mechanisms9. The main non-genomic mechanisms involve the activation of endothelial nitric oxide (NO) synthase and NO synthesis, which produce an increase in noradrenergic neurotransmission in the airway vasculature, with a consequent reduction in airway blood flow10. The decrease in airway blood flow is a desirable effect in asthmatic patients, given that they have significantly increased blood flow in the airway mucosa11.
Therefore, the use of ICS for treating patients with acute asthma has become a subject of interest in recent years. There are reports showing the clear efficacy of ICS in the management of acute asthma when compared with a placebo8,12. In a recent systematic review with a meta-analysis that compared the efficacy of ICS with SC for acute asthma in children consulting in the ED or the equivalent, we found no significant differences between ICS and SC in terms of hospital admission rates, unscheduled visits for asthma symptoms, or need for an additional course of SC12. However, only a few studies have investigated the possibility of a beneficial effect of ICS added to SC, and the results have been conflicting, as was stated in a systematic review published in 2012, where only two RCTs carried out exclusively in a pediatric population were included8.
Thus the present systematic review aims at updating and evaluating the available evidence for the efficacy of ICS (via nebulizer or metered dose inhaler [MDI]) in addition to SC compared to the standard therapy with SC for treating pediatric patients with acute asthma in the ED or during hospitalization.